There has been a major effort in recent years to discover new drug compounds that act by stimulating certain key aspects of the immune system, as well as by suppressing certain other aspects. These compounds, referred to herein as immune modulators, may be useful for treating a wide variety of diseases and conditions. For example, certain immune modulators may be useful for treating viral diseases (e.g., human papilloma virus, hepatitis, herpes), neoplasias (e.g., basal cell carcinoma, squamous cell carcinoma, actinic keratosis, melanoma), and Th2-mediated diseases (e.g., asthma, allergic rhinitis, atopic dermatitis, multiple sclerosis), and are also useful as vaccine adjuvants.
Several polysaccharides (carbohydrate polymers) of mannose (e.g., mannans), β(1,3) glucose (e.g., glucans), β(1,4) acetylated mannose (acemannans), β(1,4) N-acetyl-glucosamine (chitins), and heteropolysaccharides, such as rhamnogalacturonans (pectins), have been shown to stimulate the immune system.
Binding of polysaccharides to C-type lectin receptors induces immunostimulation, as shown by the increase in phagocytosis, proliferative responses, release of cytokines, and other activities of the immune system. Because of this immunostimulatory activity, these polysaccharides have been proposed for use in vaccine compositions. Of particular interest is mannan.
Mannan is a polymannose recognized by C-type lectin receptors, such as the mannose receptor (CD206) and DC-SIGN (CD209). Because of their presence on antigen-presenting cells, these receptors have been characterized for their uptake of mannose, fucose or glucose containing compounds. Binding of mannan to the mannose receptor for instance, induces endocytosis, followed by its delivery into the endosomal pathway. Early studies on mannnosylated antigens indicated that the presence of mannose residues on antigens greatly enhanced antigen-uptake and major histocompatibility complex (MHC) class II-restricted antigen presentation by dendritic cells (DCs). Conjugation of mannan to at least one antigen also enhances its uptake and presentation.
There is a need for further immunomodulatory and vaccine compositions for use in the treatment or prevention of diseases, as well as reliable methods for the preparation thereof. Furthermore, in view of the great therapeutic potential for immune modulators, and despite the work that has already been done, there is a substantial ongoing need to expand their uses and therapeutic benefits.